Q9BY41 (HDAC8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone deacetylase 8
Short name=HD8
EC=3.5.1.98

Gene names

Name:	HDAC8
Synonyms:	HDACL1
ORF Names:	CDA07

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	377 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. Ref.1 Ref.2 Ref.3 Ref.11 Ref.16
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Cofactor	Binds 1 divalent metal cation per subunit.
Enzyme regulation	Its activity is inhibited by trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4-phenylacetyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4-dimethylamino-N-(6-hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4-dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl-benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'-hydroxyamide (CRA-A) and butyrate. Ref.17
Subunit structure	Interacts with PEPB2-MYH11, a fusion protein consisting of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11 produced by the inversion Inv16(p13q22), a translocation associated with acute myeloid leukemia of M4EO subtype. The PEPB2-MYH1 fusion protein also interacts with RUNX1, a well known transcriptional regulator, suggesting that the interaction with HDAC8 may participate in the conversion of RUNX1 into a constitutive transcriptional repressor. Interacts with CBFA2T3. Interacts with phosphorylated SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated degradation. Associates with alpha-SMA (smooth muscle alpha-actin). Ref.9 Ref.10 Ref.14
Subcellular location	Nucleus. Cytoplasm. Note: Excluded from the nucleoli. Found in the cytoplasm of cells showing smooth muscle differentiation. Ref.11 Ref.12 Ref.13
Tissue specificity	Weakly expressed in most tissues. Expressed at higher level in heart, brain, kidney and pancreas and also in liver, lung, placenta, prostate and kidney. Ref.2 Ref.11 Ref.12 Ref.13
Post-translational modification	Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4. Ref.11 Ref.17
Involvement in disease	Cornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Wilson-Turner X-linked mental retardation syndrome (WTS) [MIM:309585]: A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15
Sequence similarities	Belongs to the histone deacetylase family. HD type 1 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Mental retardation Obesity
Ligand	Metal-binding
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chromatin assembly or disassembly Traceable author statement Ref.1. Source: ProtInc histone H3 deacetylation Inferred from electronic annotation. Source: GOC histone H4 deacetylation Inferred from electronic annotation. Source: GOC negative regulation of transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc regulation of cohesin localization to chromatin Inferred from mutant phenotype Ref.16. Source: UniProtKB sister chromatid cohesion Inferred from mutant phenotype Ref.16. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Traceable author statement PubMed 12711221. Source: UniProtKB histone deacetylase complex Traceable author statement PubMed 12711221. Source: UniProtKB nuclear chromosome Traceable author statement Ref.1. Source: ProtInc
Molecular_function	NAD-dependent histone deacetylase activity (H3-K14 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K18 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K9 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H4-K16 specific) Inferred from electronic annotation. Source: EC histone deacetylase activity Traceable author statement PubMed 12711221. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW transcription factor binding Traceable author statement PubMed 12711221. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BY41-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9BY41-2)

The sequence of this isoform differs from the canonical sequence as follows:
     248-272: LKEVYQAFNPKAVVLQLGADTIAGD → RTSCPKSRPVEAAAAACLPHLHSLV
     273-377: Missing.

Note: Derived from EST data.

Isoform 3 (identifier: Q9BY41-3)

The sequence of this isoform differs from the canonical sequence as follows:
     147-163: DEASGFCYLNDAVLGIL → RDVCVCGTLQGILKKSK
     164-377: Missing.

Isoform 4 (identifier: Q9BY41-4)

The sequence of this isoform differs from the canonical sequence as follows:
     56-146: Missing.

Note: No experimental confirmation available.

Isoform 5 (identifier: Q9BY41-5)

The sequence of this isoform differs from the canonical sequence as follows:
     246-272: SVLKEVYQAFNPKAVVLQLGADTIAGD → RYEPPAPNPGL
     273-377: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 377

377

Histone deacetylase 8

PRO_0000114708

Regions

Region

14 – 324

311

Histone deacetylase

Sites

Active site

143

1

Proton acceptor Ref.19

Metal binding

178

1

Divalent metal cation

Metal binding

180

1

Divalent metal cation

Metal binding

267

1

Divalent metal cation

Binding site

101

1

Substrate

Binding site

151

1

Substrate; via carbonyl oxygen

Binding site

306

1

Substrate

Amino acid modifications

Modified residue

39

1

Phosphoserine Ref.17

Natural variations

Alternative sequence

56 – 146

91

Missing in isoform 4.

VSP_043426

Alternative sequence

147 – 163

17

DEASG…VLGIL → RDVCVCGTLQGILKKSK in isoform 3.

VSP_007174

Alternative sequence

164 – 377

214

Missing in isoform 3.

VSP_007175

Alternative sequence

246 – 272

27

SVLKE…TIAGD → RYEPPAPNPGL in isoform 5.

VSP_043427

Alternative sequence

248 – 272

25

LKEVY…TIAGD → RTSCPKSRPVEAAAAACLPH LHSLV in isoform 2.

VSP_007176

Alternative sequence

273 – 377

105

Missing in isoform 2 and isoform 5.

VSP_007177

Natural variant

180

1

H → R in CDLS5. Ref.16

VAR_069140

Natural variant

311

1

T → M in CDLS5. Ref.16

VAR_069141

Natural variant

320

1

G → R in CDLS5. Ref.16

VAR_069142

Natural variant

334

1

H → R in CDLS5. Ref.16

VAR_069143

Experimental info

Mutagenesis

39

1

S → A: Enhances the deacetylase activity. Ref.2 Ref.11

Mutagenesis

39

1

S → E: Decreases the deacetylase activity. Ref.2 Ref.11

Mutagenesis

101

1

D → A: Complete loss of catalytical activity. Complete loss of catalytical activity; when associated with F-306. Ref.2 Ref.18 Ref.19

Mutagenesis

101

1

D → E: Partial loss of catalytical activity. Ref.2 Ref.18 Ref.19

Mutagenesis

101

1

D → L: Complete loss of catalytical activity. Ref.2 Ref.18 Ref.19

Mutagenesis

101

1

D → N: Almost complete loss of catalytical activity. Ref.2 Ref.18 Ref.19

Mutagenesis

142 – 143

2

HH → AA: Strongly reduces histone deacetylase activity. Ref.2 Ref.19

Mutagenesis

143

1

H → A: Loss of catalytic activity. Ref.2 Ref.19

Mutagenesis

306

1

Y → F: Loss of catalytic activity. Complete loss of catalytic activity; when associated with A-101. Ref.2 Ref.18

Sequence conflict

31

1

L → P in AAH50433. Ref.8

Sequence conflict

179

1

L → V no nucleotide entry Ref.4

Sequence conflict

223

1

R → W in AAF73428. Ref.2

Secondary structure

1

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377

Helix Strand Turn

Details...

Beta strand

17 – 19

3

Helix

22 – 28

7

Beta strand

31 – 34

4

Helix

37 – 47

11

Helix

50 – 53

4

Beta strand

54 – 57

4

Helix

64 – 67

4

Turn

68 – 70

3

Helix

73 – 85

13

Beta strand

87 – 89

3

Turn

91 – 97

7

Beta strand

99 – 102

4

Helix

108 – 127

20

Beta strand

128 – 130

3

Beta strand

132 – 136

5

Beta strand

153 – 155

3

Helix

157 – 165

9

Turn

166 – 168

3

Beta strand

172 – 176

5

Beta strand

178 – 180

3

Helix

183 – 188

6

Turn

189 – 191

3

Beta strand

193 – 202

10

Beta strand

207 – 209

3

Helix

220 – 222

3

Beta strand

225 – 231

7

Helix

237 – 255

19

Beta strand

258 – 263

6

Helix

266 – 268

3

Helix

281 – 292

12

Beta strand

297 – 301

5

Helix

308 – 323

16

Helix

337 – 340

4

Turn

341 – 343

3

Helix

359 – 373

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 11, 2003. Version 2. Checksum: CAA1B91894FB5013	FASTA	377	41,758
	10 20 30 40 50 60 MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI 130 140 150 160 170 180 TAAQCLIDGM CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFE RILYVDLDLH 190 200 210 220 230 240 HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDVSDVGLG KGRYYSVNVP IQDGIQDEKY 250 260 270 280 290 300 YQICESVLKE VYQAFNPKAV VLQLGADTIA GDPMCSFNMT PVGIGKCLKY ILQWQLATLI 310 320 330 340 350 360 LGGGGYNLAN TARCWTYLTG VILGKTLSSE IPDHEFFTAY GPDYVLEITP SCRPDRNEPH 370 RIQQILNYIK GNLKHVV
	Isoform 2 [UniParc]. Checksum: 060E9B19659F4A91	FASTA	272	29,944
	10 20 30 40 50 60 MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI 130 140 150 160 170 180 TAAQCLIDGM CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFE RILYVDLDLH 190 200 210 220 230 240 HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDVSDVGLG KGRYYSVNVP IQDGIQDEKY 250 260 270 YQICESVRTS CPKSRPVEAA AAACLPHLHS LV
	Isoform 3 [UniParc]. Checksum: 06E2B3E76A5D6B0D	FASTA	163	17,880
	10 20 30 40 50 60 MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI 130 140 150 160 TAAQCLIDGM CKVAINWSGG WHHAKKRDVC VCGTLQGILK KSK
	Isoform 4 [UniParc]. Checksum: B69361BAC77E90E2	FASTA	286	31,935
	10 20 30 40 50 60 MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRDEASG 70 80 90 100 110 120 FCYLNDAVLG ILRLRRKFER ILYVDLDLHH GDGVEDAFSF TSKVMTVSLH KFSPGFFPGT 130 140 150 160 170 180 GDVSDVGLGK GRYYSVNVPI QDGIQDEKYY QICESVLKEV YQAFNPKAVV LQLGADTIAG 190 200 210 220 230 240 DPMCSFNMTP VGIGKCLKYI LQWQLATLIL GGGGYNLANT ARCWTYLTGV ILGKTLSSEI 250 260 270 280 PDHEFFTAYG PDYVLEITPS CRPDRNEPHR IQQILNYIKG NLKHVV
	Isoform 5 [UniParc]. Checksum: 175AB23C2589926F	FASTA	256	28,353
	10 20 30 40 50 60 MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI 130 140 150 160 170 180 TAAQCLIDGM CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFE RILYVDLDLH 190 200 210 220 230 240 HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDVSDVGLG KGRYYSVNVP IQDGIQDEKY 250 YQICERYEPP APNPGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor." Hu E., Chen Z., Fredrickson T., Zhu Y., Kirkpatrick R., Zhang G.-F., Johanson K., Sung C.-M., Liu R., Winkler J. J. Biol. Chem. 275:15254-15264(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, FUNCTION. Tissue: Kidney.
[2]	"Cloning and characterization of a novel human histone deacetylase, HDAC8." Buggy J.J., Sideris M.L., Mak P., Lorimer D.D., McIntosh B., Clark J.M. Biochem. J. 350:199-205(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, MUTAGENESIS OF 142-HIS-HIS-143. Tissue: Uterus.
[3]	"Cloning and characterization of human histone deacetylase 8." Van den Wyngaert I., de Vries W., Kremer A., Neefs J.-M., Verhasselt P., Luyten W.H.M.L., Kass S.U. FEBS Lett. 478:77-83(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, FUNCTION. Tissue: Heart.
[4]	"Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia." McDonell N., Ramser J., Francis F., Vinet M.-C., Rider S., Sudbrak R., Riesselman L., Yaspo M.-L., Reinhardt R., Monaco A.P., Ross F., Kahn A., Kearney L., Buckle V., Chelly J. Genomics 64:221-229(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"A novel gene expressed in human pheochromocytoma." Li Y., Huang Q., Peng Y., Song H., Yu Y., Xu S., Ren S., Chen Z., Han Z. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Pheochromocytoma.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5). Tissue: Colon and Small intestine.
[7]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[9]	"ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain." Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W. Mol. Cell. Biol. 21:6470-6483(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CBFA2T3.
[10]	"The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain." Durst K.L., Lutterbach B., Kummalue T., Friedman A.D., Hiebert S.W. Mol. Cell. Biol. 23:607-619(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEPB2-MYH11 FUSION PROTEIN.
[11]	"Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A." Lee H., Rezai-Zadeh N., Seto E. Mol. Cell. Biol. 24:765-773(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY PKA, MUTAGENESIS OF SER-39, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[12]	"Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility." Waltregny D., Glenisson W., Tran S.L., North B.J., Verdin E., Colige A., Castronovo V. FASEB J. 19:966-968(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[13]	"Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus." de Leval L., Waltregny D., Boniver J., Young R.H., Castronovo V., Oliva E. Am. J. Surg. Pathol. 30:319-327(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[14]	"Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation." Lee H., Sengupta N., Villagra A., Rezai-Zadeh N., Seto E. Mol. Cell. Biol. 26:5259-5269(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMG5.
[15]	"X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face." Harakalova M., van den Boogaard M.J., Sinke R., van Lieshout S., van Tuil M.C., Duran K., Renkens I., Terhal P.A., de Kovel C., Nijman I.J., van Haelst M., Knoers N.V., van Haaften G., Kloosterman W., Hennekam R.C., Cuppen E., Ploos van Amstel H.K. J. Med. Genet. 49:539-543(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN WTS.
[16]	"HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle." Deardorff M.A., Bando M., Nakato R., Watrin E., Itoh T., Minamino M., Saitoh K., Komata M., Katou Y., Clark D., Cole K.E., De Baere E., Decroos C., Di Donato N., Ernst S., Francey L.J., Gyftodimou Y., Hirashima K. , Hullings M., Ishikawa Y., Jaulin C., Kaur M., Kiyono T., Lombardi P.M., Magnaghi-Jaulin L., Mortier G.R., Nozaki N., Petersen M.B., Seimiya H., Siu V.M., Suzuki Y., Takagaki K., Wilde J.J., Willems P.J., Prigent C., Gillessen-Kaesbach G., Christianson D.W., Kaiser F.J., Jackson L.G., Hirota T., Krantz I.D., Shirahige K. Nature 489:313-317(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, VARIANTS CDLS5 ARG-180; MET-311; ARG-320 AND ARG-334.
[17]	"Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases." Somoza J.R., Skene R.J., Katz B.A., Mol C., Ho J.D., Jennings A.J., Luong C., Arvai A., Buggy J.J., Chi E., Tang J., Sang B.-C., Verner E., Wynands R., Leahy E.M., Dougan D.R., Snell G., Navre M. , Knuth M.W., Swanson R.V., McRee D.E., Tari L.W. Structure 12:1325-1334(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH TSA; SAHA; MS-344; CRA-A AND DIVALENT METAL CATION, ENZYME REGULATION, PHOSPHORYLATION AT SER-39.
[18]	"Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex." Vannini A., Volpari C., Gallinari P., Jones P., Mattu M., Carfi A., De Francesco R., Steinkuehler C., Di Marco S. EMBO Rep. 8:879-884(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH DIVALENT METAL CATION, MUTAGENESIS OF ASP-101 AND TYR-306.
[19]	"Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors." Dowling D.P., Gantt S.L., Gattis S.G., Fierke C.A., Christianson D.W. Biochemistry 47:13554-13563(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) IN COMPLEXES WITH PEPTIDE SUBSTRATE; SAHA; TSA; M-344 AND APHA, ACTIVE SITE, MUTAGENESIS OF ASP-101 AND HIS-143.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF230097 mRNA. Translation: AAF73076.1.
AF245664 mRNA. Translation: AAF73428.1.
AJ277724 mRNA. Translation: CAB90213.1.
AK296641 mRNA. Translation: BAG59242.1.
AK300895 mRNA. Translation: BAG62534.1.
AA376331 mRNA. No translation available.
AI159768 mRNA. No translation available.
T99283 mRNA. No translation available.
AF212246 mRNA. Translation: AAK14930.1.
AL133500 Genomic DNA. No translation available.
BX295542 Genomic DNA. No translation available.
BC050433 mRNA. Translation: AAH50433.1.

IPI

IPI00245706.
IPI00515065.
IPI00645124.
IPI00647323.
IPI00747259.

RefSeq

NP_001159890.1. NM_001166418.1.
NP_001159891.1. NM_001166419.1.
NP_060956.1. NM_018486.2.

UniGene

Hs.310536.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T64	X-ray	1.90	A/B	1-377	[»]
1T67	X-ray	2.31	A	1-377	[»]
1T69	X-ray	2.91	A	1-377	[»]
1VKG	X-ray	2.20	A/B	1-377	[»]
1W22	X-ray	2.50	A/B	1-377	[»]
2V5W	X-ray	2.00	A/B	1-377	[»]
2V5X	X-ray	2.25	A/B	1-377	[»]
3EW8	X-ray	1.80	A	1-377	[»]
3EWF	X-ray	2.50	A/B/C/D	1-377	[»]
3EZP	X-ray	2.65	A/B	1-377	[»]
3EZT	X-ray	2.85	A/B	1-377	[»]
3F06	X-ray	2.55	A/B	1-377	[»]
3F07	X-ray	3.30	A/B/C	1-377	[»]
3F0R	X-ray	2.54	A/B/C	1-377	[»]
3MZ3	X-ray	3.20	A/B	1-377	[»]
3MZ4	X-ray	1.84	A/B	1-377	[»]
3MZ6	X-ray	2.00	A	1-377	[»]
3MZ7	X-ray	1.90	A	1-377	[»]
3RQD	X-ray	2.14	A/B	1-377	[»]
3SFF	X-ray	2.00	A	1-377	[»]
3SFH	X-ray	2.70	A	1-377	[»]

ProteinModelPortal

Q9BY41.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-5207407.

STRING

9606.ENSP00000362674.

PTM databases

PhosphoSite

Q9BY41.

Polymorphism databases

DMDM

29839394.

Proteomic databases

PaxDb

Q9BY41.

PRIDE

Q9BY41.

Protocols and materials databases

DNASU

55869.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373573; ENSP00000362674; ENSG00000147099.
ENST00000373589; ENSP00000362691; ENSG00000147099.
ENST00000439122; ENSP00000414486; ENSG00000147099.
ENST00000599422; ENSP00000472595; ENSG00000268498.
ENST00000600470; ENSP00000471156; ENSG00000268498.
ENST00000601791; ENSP00000471979; ENSG00000268498.

GeneID

55869.

KEGG

hsa:55869.

UCSC

uc004eau.3. human.

Organism-specific databases

CTD

55869.

GeneCards

GC0XM071549.

HGNC

HGNC:13315. HDAC8.

HPA

HPA048560.

MIM

300269. gene.
300882. phenotype.
309585. phenotype.

neXtProt

NX_Q9BY41.

Orphanet

199. Cornelia de Lange syndrome.

PharmGKB

PA37766.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0123.

HOGENOM

HOG000225180.

HOVERGEN

HBG057112.

InParanoid

Q9BY41.

KO

K11405.

OMA

IDLDLHH.

OrthoDB

EOG405S1D.

PhylomeDB

Q9BY41.

Enzyme and pathway databases

BRENDA

3.5.1.98. 2681.

Pathway_Interaction_DB

hdac_classi_pathway. Signaling events mediated by HDAC Class I.

Reactome

REACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

SABIO-RK

Q9BY41.

Gene expression databases

ArrayExpress

Q9BY41.

Bgee

Q9BY41.

CleanEx

HS_HDAC8.

Genevestigator

Q9BY41.

GermOnline

ENSG00000147099. Homo sapiens.

Family and domain databases

Gene3D

3.40.800.20. 1 hit.

InterPro

IPR000286. His_deacetylse.
IPR003084. His_deacetylse_1.
IPR023801. His_deacetylse_dom.
[Graphical view]

PANTHER

PTHR10625. PTHR10625. 1 hit.

Pfam

PF00850. Hist_deacetyl. 1 hit.
[Graphical view]

PIRSF

PIRSF037913. His_deacetylse_1. 1 hit.

PRINTS

PR01270. HDASUPER.
PR01271. HISDACETLASE.

ProtoNet

Search...

Other

BindingDB

Q9BY41.

ChEMBL

CHEMBL3192.

ChiTaRS

HDAC8. human.

DrugBank

DB02546. Vorinostat.

EvolutionaryTrace

Q9BY41.

GenomeRNAi

55869.

NextBio

61182.

SOURCE

Search...

Entry information

Entry name

HDAC8_HUMAN

Accession

Primary (citable) accession number: Q9BY41
Secondary accession number(s): A6NET3 , A8MQ62, B4DKN0, B4DV22, Q86VC8, Q9NP76, Q9NYH4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 11, 2003
Last sequence update:	April 11, 2003
Last modified:	May 1, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.